RT Journal Article
SR Electronic
T1 Recapitulation of the evolution of biosynthetic gene clusters reveals hidden chemical diversity on bacterial genomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 020503
DO 10.1101/020503
A1 Pablo Cruz-Morales
A1 Christian E. Martínez-Guerrero
A1 Marco A. Morales-Escalante
A1 Luis Yáñez-Guerra
A1 Johannes Florian Kopp
A1 Jörg Feldmann
A1 Hilda E. Ramos-Aboites
A1 Francisco Barona-Gómez
YR 2015
UL http://biorxiv.org/content/early/2015/07/06/020503.abstract
AB Natural products have provided humans with antibiotics for millennia. However, a decline in the pace of chemical discovery exerts pressure on human health as antibiotic resistance spreads. The empirical nature of current genome mining approaches used for natural products research limits the chemical space that is explored. By integration of evolutionary concepts related to emergence of metabolism, we have gained fundamental insights that are translated into an alternative genome mining approach, termed EvoMining. As the founding assumption of EvoMining is the evolution of enzymes, we solved two milestone problems revealing unprecedented conversions. First, we report the biosynthetic gene cluster of the ‘orphan’ metabolite leupeptin in Streptomyces roseus. Second, we discover an enzyme involved in formation of an arsenic-carbon bond in Streptomyces coelicolor and Streptomyces lividans. This work provides evidence that bacterial chemical repertoire is underexploited, as well as an approach to accelerate the discovery of novel antibiotics from bacterial genomes.